This is a 3-year R01 proposal to develop techniques and instrumentation for real time guidance of stereotactic needle biopsies of the breast for microcalcifications using Raman spectroscopy. Microcalcifications are deposits of calcium mineral salts within breast tissue. When seen at mammography, they geographically localize the most clinically significant abnormality and are, therefore, a target for subsequent needle biopsy. Raman spectroscopy uses light to obtain a chemical fingerprint of breast tissue that can be analyzed quantitatively to render an objective, parameter-based diagnosis. It is exquisitely sensitive to calcium- containing minerals, and thus can be used to detect and localize microcalcifications in the breast. This can be done in vivo, in real-time, in a non-destructive manner, via optical fiber probes through existing needle biopsy devices. We propose to develop Raman spectroscopy as a clinical tool to provide real-time feedback to the radiologist to improve retrieval of microcalcifications during stereotactic breast needle biopsies. Such a clinical tool should: reduce the number of non-diagnostic needle biopsies and the need for follow up surgical biopsy;minimize the radiation exposure and number of tissue cores required;and significantly reduce both procedure time and patient anxiety/distress. To accomplish this we will design, fabricate and field test a compact, reliable, user friendly, portable Raman instrument and a side-viewing optical fiber Raman probe for use in conjunction with a commercial vacuum-assisted stereotactic needle biopsy system during breast biopsies performed in the outpatient setting. We will also develop objective, quantitative, parameter-based Raman spectroscopy algorithms to not only detect and localize breast tissue microcalcifications, but also classify them as type I or II and diagnose the benign or malignant lesion with which they are associated. Finally, we will conduct human studies, first a small scale proof-of-principle feasibility study and then a larger scale clinical validation study, of our Raman spectroscopy instrumentation and diagnostic algorithms in vivo in patients undergoing vacuum- assisted stereotactic needle biopsy of breast microcalcifications. PUBLIC HEALTH RELEVANCE: This research will improve public health by devising a clinical tool that will improve the diagnosis of breast cancer. This will be accomplished by developing optical instrumentation and techniques to provide real-time feedback to radiologists to improve retrieval of microcalcifications during stereotactic needle biopsies of the breast. Such a clinical tool should not only reduce the number of non-diagnostic needle biopsies and the need for follow up surgical biopsy, but also minimize the radiation exposure required and significantly reduce both procedure time and patient anxiety/distress.